DESCRIPTION: Most patients who undergo major surgery do not receive adequate treatment of their pain. They suffer needlessly because traditional approaches to the management of acute post-operative pain have focused primarily on treating the patient after surgery in an effort to reduce already established pain. It is becoming increasingly clear, however, that the very act of cutting tissue, nerve, and bone may induce long-lasting changes in central neural function that amplify post-operative pain intensity, increase the need for analgesics, and set the stage for the development of chronic, intractable pain. One of the most effective ways to prevent noxious input during surgery from reaching the spinal cord is to administer local anesthetics and opioids via the epidural route before surgery. This preventive approach to the problem of acute post-operative pain has been termed pre-emptive analgesia and its significance lies not only in the obvious immediate benefit of protecting the patient at the time of surgical trauma, but also in the possibility that such pre-treatment will attenuate the development of central sensitization and of potentially detrimental changes in immune function. The proposed study uses a three group, randomized, double-blind, placebo-controlled, cross-over design. Patients undergoing abdominal hysterectomy will receive (1) pre-incisional epidural fentanyl and lidocaine followed by post-incisional epidural saline, (2) pre-incisional epidural saline followed by post-incisional fentanyl and lidocaine, or (3) pre and post-incisional saline via a sham epidural. All patients will receive a general anesthetic. It is hypothesized that, by interrupting the transmission of noxious peri-operative inputs to the spinal cord, the pre-emptive approach will attenuate the development of central sensitization and result in reduced pain and lower requirements for morphine long after the effects of the epidural agents have worn off. This project will also examine physiological mechanisms and psychosocial moderating factors involved in pain and immune function. Finally, the study will assess the effects of pre-operative psychosocial factors on changes in immune function, pain, and post operative adjustment. The broad aim of this intervention is to increase quality of life by decreasing stress, pain, analgesic requirements, and post-operative immune suppression, possibly reducing post-surgical complications due to infections and morphine usage. The anticipated morphine-sparing effect may reduce potential adverse effects, decrease treatment costs, and shorten length of hospital stay.